Clayton State University IRB

Question 1: Does your proposed research involve human subjects?

The first thing you must determine is whether or not your research involves human subjects, either at the applicant organization or at any other performance site or collaborating institution (e.g., subcontractors, consultants).

The research described in your application may include more than one research project; thus the application may include individual projects that meet the requirements for non-exempt or exempt human subjects research, or are not defined as human subjects research.

If research activities involving human subjects are planned at any time during the proposed project period, either at the applicant organization or at any other performance site or collaborating institution, then your answer is "Yes" even if the research is exempt from regulations for the protection of human subjects.

The HHS regulations "Protection of Human Subjects" (45 CFR Part 46, administered by OHRP) define a human subject as a living individual about whom an investigator conducting research obtains:

• Data through intervention or interaction with the individual or
• Identifiable private information

Investigator: The OHRP considers the term investigator to include anyone involved in conducting the research. OHRP does not consider the act of solely providing coded private information or specimens (for example, by a tissue repository) to constitute involvement in the conduct of the research. However, if the individuals who provide coded information or specimens also collaborate on other activities related to the conduct of the research with the investigators who receive such information or specimens, they will be considered to be involved in the conduct of the research. (OHRP's Coded Specimen Guidance.)

Research: HHS regulations define research at 45 CFR 46.102(d) as follows: Research means a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute research for purposes of this policy, whether or not they are conducted or supported under a program which is considered research for other purposes. For example, some demonstration and service programs may include research activities.

Obtains: In its guidance for use of coded specimens, OHRP has determined that under the definition of human subject at 45 CFR 46.102(f), obtaining identifiable private information or identifiable specimens for research purposes constitutes human subjects research. Obtaining means receiving or accessing identifiable private information or identifiable specimens for research purposes. OHRP interprets obtaining to include an investigator's use, study, or analysis for research purposes of identifiable private information or identifiable specimens already in the possession of the investigator.

Intervention includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. (45 CFR 46.102(f))

Interaction includes communication or interpersonal contact between investigator and subject. (45 CFR 46.102(f))

Private Information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information that has been provided for specific purposes by an individual and that the individual can reasonably expect will not be made public (for example, a medical record). Private information must be individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information) in order for obtaining the information to constitute research involving human subjects. (45 CFR 46.102(f))

Individually Identifiable Private Information: According to its guidance for use of coded specimens, OHRP generally considers private information or specimens to be individually identifiable as defined at 45 CFR 46.102(f) when they can be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems. Conversely, OHRP considers private information or specimens not to be individually identifiable when they cannot be linked to specific individuals by the investigator(s) either directly or indirectly through coding systems.

Research Using Human Specimens or Data:

Regulatory requirements (Federal and state) to protect human subjects apply to a much broader range of research than many investigators realize, and researchers using human specimens and/or data are often unsure about how regulations apply to their research. Regulatory obligations to protect human subjects would apply, for example, to research that uses:

• Bodily materials, such as cells, blood or urine, tissues, organs, hair or nail clippings, from living individuals who are individually identifiable to the investigator(s), even if these materials were collected by others;
• Residual diagnostic specimens from living individuals that are individually identifiable to the investigator(s), including specimens obtained for routine patient care that would have been discarded if not used for research;
• Private information, such as medical information, about living individuals that is individually identifiable to the investigator(s), even if the information was not specifically collected for the study in question. This includes research on genetic information that can be readily associated, by the investigator(s), with identifiable living individuals.

The definition of “human subject” includes, but is not limited to, human organs, tissues, and body fluids of living individuals, as well as private graphic, written, or recorded information about living individuals, if (1) there is interaction or intervention with a living individual to obtain the specimens or data for research purposes or (2) the identity of the subjects can be readily ascertained by the investigator or other members of the research team.

Research that involves only coded private information/data or coded human biological specimens may not constitute human subjects research under the HHS human subjects regulations (45 CFR Part 46) if:

• The specimens and/or private information were not collected specifically for the currently proposed research project through an interaction/intervention with living individuals AND
• The investigator(s) (including collaborators) on the proposed research cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain (e.g., the researcher's access to subject identities is prohibited by written repository procedures and policies and/or through an agreement signed between the recipient researcher and the repository providing the specimens and/or data). (See definitions below and the following guidance from the Office for Human Research Protections (OHRP) for additional information and examples: http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf.)

Individuals who provide coded information or specimens for proposed research and who also collaborate on the research involving such information or specimens are considered to be involved in the conduct of human subjects research.

Coded: With respect to private information or human biological specimens, coded means that:

1. Identifying information (such as name or social security number) that would enable the investigator to readily ascertain the identity of the individual to whom the private information or specimens pertain has been replaced with a number, letter, symbol or combination thereof (i.e., the code); and
2. A key to decipher the code exists, enabling linkage of the identifying information with the private information or specimens.

You may find it helpful to consult the following guidance from OHRP:

• OHRP Decision Charts: http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.htm
• OHRP Policy on Coded Specimens and Data: http://www.hhs.gov/ohrp/humansubjects/guidance/cdebiol.pdf
• OHRP Guidance on Repositories: http://www.hhs.gov/ohrp/humansubjects/guidance/reposit.htm; http://www.hhs.gov/ohrp/humansubjects/guidance/guid1223.pdf

With regard to the engagement of performance sites in proposed human subjects research, you may find it helpful to consult the following:

• OHRP Memo on Engagement: http://www.hhs.gov/ohrp/humansubjects/assurance/engage.htm

The decisions about when research involving human specimens and/or data from subjects is considered human subjects research are complex. The OHRP recommends that institutions have policies in place that designate the individual or entity authorized to determine whether proposed research is exempt from regulatory requirements to protect human subjects and that determinations should be made by someone other than the investigator.

You need to be aware that the involvement of human subjects in non-exempt research must be approved by your IRB prior to award.

The NIH Office of Extramural Research Human Subjects website contains additional information and Frequently Asked Questions that may help investigators understand how these regulations and Guidance documents apply to their research. See http://grants.nih.gov/grants/policy/hs/index.htm.

How can you determine whether research that involves only the use of specimens and/or data from pathology archives or a specimen bank and/or data repository is human subjects research?

The research described in your application may include more than one research project; thus the application may include separate projects that meet the requirements for either human subjects research, exempt human subjects research, or are not defined as human subjects research. Examples are provided below:

• If the specimens and/or data were obtained specifically for the currently proposed research project through intervention or interaction with a living individual, then your research is human subjects research.
• If you receive or have access to individually identifiable specimens or data from living individuals (e.g., pathology or medical records), your proposed research is human subjects research.
• If you receive or have access to existing individually identifiable private information or identifiable specimens from living individuals (e.g., pathology or medical records), but you as the investigator or your collaborator record the information in such a manner that you cannot subsequently access or obtain direct or indirect identifiers that are linked to the subjects the research project that you conduct using data recorded in this manner meets the requirements of Exemption 4. If you will retain or can access any identifiers, the research project is not exempt under Exemption 4.
• If you are using specimens and/or data and neither you nor your collaborators can identify the subjects from whom the specimens and/or data were obtained either directly or indirectly through coding systems, the HHS human subjects regulations (45 CFR Part 46) do not apply at all.
• If your research involves only coded private information/data or coded specimens, OHRP does not consider this research to involve human subjects as defined under the HHS Protection of Human Subjects Regulations (45 CFR Part 46.102(f)) if the following conditions are both met:
  • the private information/data or specimens were not collected specifically for the currently proposed research project through an interaction or intervention with living individuals; and
  • the investigator(s) cannot readily ascertain the identity of the individual(s) to whom the coded private information or specimens pertain because, for example:
    1. the key to decipher the code is destroyed before the research begins;
    2. the investigators and the holder of the key enter into an agreement prohibiting the release of the key to the investigators under any circumstances, until the individuals are deceased;
    3. there are IRB-approved written policies and operating procedures for a repository or data management center that prohibit the release of the key to the investigators under any circumstances, until the individuals are deceased; or
    4. there are other legal requirements prohibiting the release of the key to the investigators, until the individuals are deceased.

What is not human subjects research under HHS regulations at 45 CFR Part 46?

• Research that does not involve intervention or interaction with living individuals, or identifiable private information is not human subjects research (see definitions),
• Research that only proposes the use of cadaver specimens is not human subjects research, because human subjects are defined as "living individuals." The use of cadaver specimens is not regulated by 45 CFR Part 46, but may be governed by other federal, state and local laws.

Guidance and Additional Instructions

If you answered "No" to Question 1, then proceed to Scenario A.

If you answered "Yes" to Question 1, then you may need to determine whether your research meets the criteria for an exemption from the Human Subjects Protection requirements. Proceed to Question 2.

If you need to consider an alternative scenario, return to the PHS 398 Instructions Decision Table for Section E.